Evidence map›Paper›PMID 40335481›Full record

ArticleNature communications2025

A chimeric viral platform for directed evolution in mammalian cells.

Alexander J Cole, Christopher E Denes, Cesar L Moreno, Lise Hunault, Thomas Dobson, Daniel Hesselson, G Gregory Neely

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Alexander J Cole *Centenary Institute and Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Christopher E Denes *The Dr. John and Anne Chong Lab for Functional Genomics, School of Life & Environmental Sciences, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0000-0002-8669-8088
Cesar L MorenoThe Dr. John and Anne Chong Lab for Functional Genomics, School of Life & Environmental Sciences, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Lise HunaultCentenary Institute and Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Thomas DobsonCentenary Institute and Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.ORCID http://orcid.org/0009-0003-0320-4260
Daniel HesselsonCentenary Institute and Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia. d.hesselson@centenary.org.au.ORCID http://orcid.org/0000-0002-8675-9426
G Gregory NeelyThe Dr. John and Anne Chong Lab for Functional Genomics, School of Life & Environmental Sciences, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia. greg.neely@sydney.edu.au.ORCID http://orcid.org/0000-0002-1957-9732

Funding

Department of Health | National Health and Medical Research Council (NHMRC) GNT1185002, GNT1107514, GNT1158164, GNT1158165
6 · The paper itself

Abstract

Directed evolution is a process of mutation and artificial selection to breed biomolecules with new or improved activity. Directed evolution platforms are primarily prokaryotic or yeast-based, and stable mammalian systems have been challenging to establish and apply. To this end, we develop PROTein Evolution Using Selection (PROTEUS), a platform that uses chimeric virus-like vesicles to enable extended mammalian directed evolution campaigns without loss of system integrity. This platform is stable and can generate sufficient diversity for directed evolution in mammalian systems. Using PROTEUS, we alter the doxycycline responsiveness of tetracycline-controlled transactivators, generating a more sensitive TetON-4G tool for gene regulation with mammalian-specific adaptations. PROTEUS is also compatible with intracellular nanobody evolution, and we use it to evolve a DNA damage-responsive anti-p53 nanobody. Overall, PROTEUS is an efficient and stable platform to direct evolution of biomolecules within mammalian cells.

Indexed as

Directed Molecular EvolutionAnimalsHEK293 CellsHumansSingle-Domain AntibodiesTumor Suppressor Protein p53Single-Domain AntibodiesTumor Suppressor Protein p53

Identifiers

PMID40335481
PMCPMC12059018

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.